Posted by Mitch on October 25, 2001, at 0:01:27
In reply to Re: Nierenberg - Clonidine for bipolar depression? » Mitch, posted by JohnX on October 24, 2001, at 22:30:01
> Mitch,
>
> I read a paper on the proposed mechanism of
> Wellbutrin, but I don't remember the details
> off the top of my head. I believe the partial jist of
> it was that the norepinephrine **reuptake inhibition**
> causes the alpha-2 adrenoreceptors to downregulate
> long term. I.e. they become less sensitive to
> repeated exposure to norepinephrine in the synapse,
> thus boosting norepinephrine levels because of
> the reuptake inhibition but curbing
> the rate of firing of the neurons themselves due
> to the alpha-2 downregulation.Thanks John, that makes a lot of sense. I have taken Remeron at therapeutic dosages for several weeks (and Buspar for several weeks), and the hostility seemed to be exacerbated rather than reduced with time. So, this makes me wonder whether the alpha-2 receptors are indeed *downregulated* with mirtazipine and buspirone. It seems that receptor downregulation seems to be exclusively limited to agents that affect the *transporters*. Given that both these agents do not appear to block reuptake of NE as their primary mechanism. So, otherwords without downregulation of alpha-2 receptors the hostility should NOT resolve with time (seems to fit).
Mitch
poster:Mitch
thread:81697
URL: http://www.dr-bob.org/babble/20011015/msgs/82244.html